Dual role of the miR-146 family in rhinovirus-induced airway inflammation and allergic asthma exacerbation
Abstract
Rhinovirus (RV) infections are associated with asthma exacerbations. MicroRNA‐146a and microRNA‐146b (miR‐146a/b) are anti‐inflammatory miRNAs that suppress signaling through the nuclear factor kappa B (NF‐κB) pathway and inhibit pro‐inflammatory chemokine production in primary human bronchial epithelial cells (HBECs). In the current study, we aimed to explore whether miR‐146a/b could regulate cellular responses to RVs in HBECs and airways during RV‐induced asthma exacerbation. We demonstrated that expression of miR‐146a/b and pro‐inflammatory chemokines was increased in HBECs and mouse airways during RV infection. However, transfection with cell‐penetrating peptide (CPP)‐miR‐146a nanocomplexes before infection with RV significantly reduced the expression of the pro‐inflammatory chemokines CCL5, IL‐8 and CXCL1, increased interferon‐λ production, and attenuated infection with the green fluorescent protein (GFP)‐expressing RV‐A16 in HBECs. Concordantly, compared to wild‐type (wt) mice, Mir146a/b−/− mice exhibited more severe airway neutrophilia and increased T helper (Th)1 and Th17 cell infiltration in response to RV‐A1b infection and a stronger Th17 response with a less prominent Th2 response in house dust mite extract (HDM)‐induced allergic airway inflammation and RV‐induced exacerbation models. Interestingly, intranasal administration of CPP‐miR‐146a nanocomplexes reduced HDM‐induced allergic airway inflammation without a significant effect on the Th2/Th1/Th17 balance in wild‐type mice. In conclusion, the overexpression of miR‐146a has a strong anti‐inflammatory effect on RV infection in HBECs and a mouse model of allergic airway inflammation, while a lack of miR‐146a/b leads to attenuated type 2 cell responses in mouse models of allergic airway inflammation and RV‐induced exacerbation of allergic airway inflammation. Furthermore, our data indicate that the application of CPP‐miR‐146a nanocomplexes has therapeutic potential for targeting airway inflammation.
Related
- Identification of a Novel Inhibitor of Human Rhinovirus Replication and Inflammation in Airway Epithelial Cells
- Cadherin-related Family Member 3 Genetics and Rhinovirus C Respiratory Illnesses
- ILC2-intrinsic IL-33 amplifies ILC2 activation and allergic lung inflammation
- Genome-Wide Transcriptomics Uncovers a Lung-to-Aorta Inflammatory Program Driving Influenza-Induced Atherosclerosis Exacerbation
- Sennoside A differentially regulates mast cell activation and attenuates gut allergic inflammation
BibTeX
@article{laanesoo2026dual,
title = {{Dual role of the miR-146 family in rhinovirus-induced airway inflammation and allergic asthma exacerbation}},
author = {A. Laanesoo and E. Urgard and K. Periyasamy and M. Laan and Y. A. Bochkov and A. Aab and N. Magilnick and M. Pooga and J. E. Gern and S. L. Johnston and J. M. Coquet and M. P. Boldin and J. Wengel and A. Altraja and G. Bochenek and B. Jakiela and A. Rebane},
journal = {Clinical and Translational Medicine},
year = {2026},
month = oct,
doi = {10.1002/ctm2.427},
url = {https://hal.science/hal-05787881v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dual role of the miR-146 family in rhinovirus-induced airway inflammation and allergic asthma exacerbation
AU - A. Laanesoo
AU - E. Urgard
AU - K. Periyasamy
AU - M. Laan
AU - Y. A. Bochkov
AU - A. Aab
AU - N. Magilnick
AU - M. Pooga
AU - J. E. Gern
AU - S. L. Johnston
AU - J. M. Coquet
AU - M. P. Boldin
AU - J. Wengel
AU - A. Altraja
AU - G. Bochenek
AU - B. Jakiela
AU - A. Rebane
PY - 2026
DA - 2026/10/09
JO - Clinical and Translational Medicine
DO - 10.1002/ctm2.427
UR - https://hal.science/hal-05787881v1
AB - Rhinovirus (RV) infections are associated with asthma exacerbations. MicroRNA‐146a and microRNA‐146b (miR‐146a/b) are anti‐inflammatory miRNAs that suppress signaling through the nuclear factor kappa B (NF‐κB) pathway and inhibit pro‐inflammatory chemokine production in primary human bronchial epithelial cells (HBECs). In the current study, we aimed to explore whether miR‐146a/b could regulate cellular responses to RVs in HBECs and airways during RV‐induced asthma exacerbation. We demonstrated that expression of miR‐146a/b and pro‐inflammatory chemokines was increased in HBECs and mouse airways during RV infection. However, transfection with cell‐penetrating peptide (CPP)‐miR‐146a nanocomplexes before infection with RV significantly reduced the expression of the pro‐inflammatory chemokines CCL5, IL‐8 and CXCL1, increased interferon‐λ production, and attenuated infection with the green fluorescent protein (GFP)‐expressing RV‐A16 in HBECs. Concordantly, compared to wild‐type (wt) mice, Mir146a/b−/− mice exhibited more severe airway neutrophilia and increased T helper (Th)1 and Th17 cell infiltration in response to RV‐A1b infection and a stronger Th17 response with a less prominent Th2 response in house dust mite extract (HDM)‐induced allergic airway inflammation and RV‐induced exacerbation models. Interestingly, intranasal administration of CPP‐miR‐146a nanocomplexes reduced HDM‐induced allergic airway inflammation without a significant effect on the Th2/Th1/Th17 balance in wild‐type mice. In conclusion, the overexpression of miR‐146a has a strong anti‐inflammatory effect on RV infection in HBECs and a mouse model of allergic airway inflammation, while a lack of miR‐146a/b leads to attenuated type 2 cell responses in mouse models of allergic airway inflammation and RV‐induced exacerbation of allergic airway inflammation. Furthermore, our data indicate that the application of CPP‐miR‐146a nanocomplexes has therapeutic potential for targeting airway inflammation.
SN - 2001-1326
ER -